Collective Uncertainty Project:
Hope for Randomised Clinical Trials in
Trauma and Orthopaedics
Kulikov Y1, Brydges S2, Girling A3, Lilford R3, Griffin D1
1
2
3
Warwick Medical School, UK
eLab, University of Warwick, UK
Public Health & Epidemiology, University of Birmingham, UK
Glossary
Collective equipoise (Freedman, 1987)
justifiable uncertainty within the medical profession about which treatment is most effective for a particular condition
implies that there is no (rational) preference whatever
Collective uncertainty
in reality collective equipoise is rarely exactly evenly balanced, but uncertainty remains about the best treatment option
though individuals may have a preference for one treatment, they are balanced by the others with the opposite view
required before any clinical trial can be approved by ethics committee
Prior probability
Prior sense of the effects of treatment(s)
Can be based entirely on expert opinion
yuri.kulikov@warwickorthopaedics.org
Randomised controlled clinical trials (RCTs)
in Trauma & Orthopaedics
produce the most reliable evidence about the effects of clinical care
but
are (very) expensive and (very) difficult for a number of reasons (McCulloch et
al, 2002)
in particular because
lack of surgeons’ individual equipoise in a specific clinical situation, which is
often rational, has been shown to be a major obstacle in participant recruitment
Collective Uncertainty Project
•
to apply Collective Uncertainty to individual clinical scenarios
•
to assess degree to which uncertainty must be present as the fundamental
criterion for eligibility for a trial
yuri.kulikov@warwickorthopaedics.org
Design (materials and methods)
Secure
website
Clinical images
Clinical
data
Interactive Voting Scale
yuri.kulikov@warwickorthopaedics.org
Design (materials and methods)
Integrated into the UK Heel Fracture Trial (UK HeFT) – conservative
versus operative treatment for displaced fractures of calcaneum
Expert panel of 10 Consultant Trauma Surgeons from 8 hospitals across
the UK
Consequent potentially eligible for randomisation clinical cases
identified via the UK HeFT published via secure online forum after
consent being obtained in 6 weeks follow up clinic or later
Surgeons alerted about new cases via email and SMS (optional) and
express their opinion online
Level of uncertainty assessed by application of 80:20 ethical uncertainty
distribution limit (Johnson et al, 1991), by accounting all votes in favour
of operative treatment (a bit better + significantly better + much better)
“strong votes” (significantly better + much better) were accounted
separately to demonstrate support or otherwise for recommendation
yuri.kulikov@warwickorthopaedics.org
Results
30 eligible cases, of those 17 (56.7%) not randomised for HeFT
4 bilateral injuries
11 declined participation
4 did not want to have surgery
5 wanted to have surgery
1 wanted to be treated privately
1 did not want to be randomised
1 randomised in error
1 had previously infected tibial plate same side (removed)
Of 13 randomised 2 (15.4%) declined intended treatment (surgery)
On average 5 surgeons voted per case (min 3, max 8)
26 cases incl. all bilateral injuries could be recommended for randomisation
Legend
chXXX – case number
Grey bars – votes by individual surgeons
Burgundy bars – cumulative average votes
yuri.kulikov@warwickorthopaedics.org
Results
3 cases the panel recommended for
non-operative treatment
CH007 – 8.4% for surgery (1.2% strong votes)
CH027 – 13.7% for surgery(1.7% strong votes)
CH014 – 15% for surgery (4% strong votes)
UK HeFT: CH007 – randomised to non-operative treatment;
1 case the panel recommended for
operative treatment
CH015 – 87% for surgery (72% strong votes)
CH015 – randomised to operative treatment;
CH014 – declined to take part (did not want surgery);CH027 – declined randomisation (treated non-operatively)
yuri.kulikov@warwickorthopaedics.org
Discussion
Pitfalls
Surgeons’ reluctance to vote (maybe
overcome if votes will be more
relevant)
Technical (PACS required in hospitals
involved; very few glitches so far,
overall simple cheap and stable
system)
Strengths
Ease of use (3-5 min to vote per case)
No geographical boundaries
Instant application in real time (48 hours
required to obtain votes)
Ethical value (randomisation only when the
panel feels appropriate; individual, personal
approach )
Measuring Collective Uncertainty in our study showed potential to DOUBLE (from
43.3% to 86.7%) patient recruitment for the UK HeFT
At the same time patients would not have been offered randomisation where current
specialist opinion (prior probability) is strongly in favour of one or another treatment
Broader inclusion criteria possible, because every patient is assessed for
randomisation individually
Both surgeon and patient are supported in their decision by an expert panel
The Uncertainty Measurement is an opinion (prior probability); the final decision
remains between a treating surgeon and a patient
yuri.kulikov@warwickorthopaedics.org
Conclusion
We propose Measurement of Collective Uncertainty to be introduced into Surgical
RCTs where decision about randomisation is especially challenging (operative vs
non-operative; standard against new but popular well-marketed treatments etc)
It is possible to set up international expert panels to suite international studies
“Empowering choice will be given precedence by those who, like me [us], think
the obligation to respect individual autonomy outweighs the common good in all
but the most extreme cases…” (Lilford, 2003)
References
•
•
•
•
Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-5
Johnson N, Lilford RJ, Brazier W. At what level of collective equipoise does a clinical trial become
ethical. Journal of Medical Ethics 1991;17:30-34
Lilford RJ. Ethics of clinical trials from a bayesian and decision analytic perspective: whose equipoise
is it anyway? BMJ 2003;326:980-1
McCulloch P, Taylor I, Sasako M, Lovett B, Griffin D. Randomised trials in surgery: problems and
possible solutions. BMJ 2002;324:1448-51
yuri.kulikov@warwickorthopaedics.org
Warwick
Medical School
University Hospitals
of Coventry and
Warwickshire
yuri.kulikov@warwickorthopaedics.org